Investigating how a test drug alters the reaction of a site-directed electrophile with a receptor is a powerful method for determining whether the drug acts competitively or allosterically, provided that the binding site of the electrophile is known. In this study, therefore, we mutated nucleophilic residues near and within the orthosteric pockets of M(1) and M(2) muscarinic receptors to identi...

Nitrogen mustards alkylate DNA primarily at the N7 position of guanine. Using an approach analogous to that of the Maxam-Gilbert procedure for DNA sequence analysis, we have examined the relative frequencies of alkylation for a number of nitrogen mustards at different guanine-N7 sites on a DNA fragment of known sequence. Most nitrogen mustards were found to have similar patterns of alkylation, ...

The nucleophilicity of transition metal thiolates is well-documented. Biologically relevant electrophilic substrates include oxygen or oxygen-transfer agents (such as H2O2) and alkylation agents (such as CH3I). Nature makes use of the latter with Zn-containing de-alkylation proteins such as the Ada repair mechanism and the former in the case of the post-translationally modified active form of N...

Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reduc...

1. A quantitative study was made of the relationship between survival of colony-forming ability in Escherichia coli strains B/r and B(s-1) and the extents of alkylation of cellular DNA, RNA and protein after treatment with mono- or di-functional sulphur mustards, methyl methanesulphonate or iodoacetamide. 2. The mustards and methyl methanesulphonate react with nucleic acids in the cells, in the...

although several methods for the preparation of 4o propargyl indole derivatives have been published, this synthetic transformation is complicated by the tendency of 3o propargyl alcohols to form allenium intermediates in acidic media.  it is therefore a challenge to find an efficient method for the c-3 propargylation of indoles with 3° propargylic alcohols.  in this paper we wish to report on t...

An asymmetric alkylation-ring-closing metathesis strategy was developed for the construction of a,a’-disubstituted medium ring ethers. The approach features an asymmetric alkylation of highly functionalized a-alkoxy acyl oxazolidinones followed by ring closure effected by Grubbs’ ruthenium catalyst. The relationship between diene conformation and the rate of ring-closure was examined.

A series of simple heteroarylidene malonate-type bis(oxazoline) ligands 4 and 5 were applied to the palladium-catalyzed allylic alkylation reaction, and the ligand 4a bearing a phenyl group afforded excellent enantioselectivity (up to 96% ee) for the allylic alkylation product. Other substrates were also examined, giving the allylic alkylated products in high yield but with poor ee values.

We report the formation of a highly unusual fused, tricyclic purine derivative via N3 alkylation of 9-propargyladenine, upon activation of the acetylenic triple bond by Ag(I) ions. The participation of silver ions in this process might offer newer design paradigms for minor groove N3 DNA alkylation, antibacterial and anticancer agents.